Nanomaterials Based on DNA

Seeman, Nadrian C.

doi:10.1146/annurev-biochem-060308-102244

Cited by 936 publications

(729 citation statements)

References 96 publications

(140 reference statements)

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“…The exquisite engineerability of a DNA-based synthetic host scaffold 23,35 or tools to interrogate biological phenomena both in living cells and whole organisms.…”

Section: Discussionmentioning

confidence: 99%

A synthetic icosahedral DNA-based host–cargo complex for functional in vivo imaging

et al. 2011

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The encapsulation of molecular cargo within well-defined supramolecular architectures is highly challenging. Synthetic hosts are desirable because of their well-defined nature and addressability. Encapsulation of biomacromolecules within synthetic hosts is especially challenging because of the former's large size, sensitive nature, retention of functionality postencapsulation and demonstration of control over the cargo. Here we encapsulate a fluorescent biopolymer that functions as a pH reporter within synthetic, DNA-based icosahedral host without molecular recognition between host and cargo. Only those cells bearing receptors for the DNA casing of the host-cargo complex engulf it. We show that the encapsulated cargo is therefore uptaken cell specifically in Caenorhabditis elegans. Retention of functionality of the encapsulated cargo is quantitatively demonstrated by spatially mapping pH changes associated with endosomal maturation within the coelomocytes of C. elegans. This is the first demonstration of functionality and emergent behaviour of a synthetic host-cargo complex in vivo.

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“…The exquisite engineerability of a DNA-based synthetic host scaffold 23,35 or tools to interrogate biological phenomena both in living cells and whole organisms.…”

Section: Discussionmentioning

confidence: 99%

A synthetic icosahedral DNA-based host–cargo complex for functional in vivo imaging

et al. 2011

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“…By taking advantage of the high versatility and designability of DNA chemistry [9][10][11][12][13][14][15][16][17][18][19] several groups have recently developed pH-triggered DNA-based probes or nanomachines [20][21][22][23][24][25][26][27][28][29][30] . Such probes typically exploit DNA secondary structures that display pH-dependence due to the presence of specific protonation sites.…”

Section: Introductionmentioning

confidence: 99%

Programmable pH-Triggered DNA Nanoswitches

2014

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ABSTRACT:Here we have rationally designed a tunable DNA-based nanoswitch whose closing/opening can be triggered over specific different pH windows. This nanoswitch forms an intramolecular triplex DNA structure through pH-sensitive parallel Hoogsteen interactions. We demonstrate that by simply changing the relative content of TAT/CGC triplets in the switch we can rationally tune its pH-dependence over more than 5 pH units. By using a combination of such nanowitches with different pH sensitivity, we also demonstrate how we can engineer a pH nanosensor that can precisely monitor pH variations over 5.5 units of pH. With their fast response time (<200 msec) and high reversibility, these pH-triggered nanoswitches appear particularly suitable for applications ranging from the real-time monitoring of pH changes in-vivo to the development of pH sensitive smart nanomaterial.Nature often employs finely pH-regulated biomolecules to modulate and tune a number of biological activities 1 ranging from enzyme catalysis 2 to protein folding 3 , membrane function 4 and apoptosis 5 . For these reasons, developing probes, switches or nanomaterials that are able to respond to specific pH changes should prove of utility for several applications in the fields of in-vivo imaging, clinical diagnostics, and drug-delivery [6][7][8] .By taking advantage of the high versatility and designability of DNA chemistry 9-19 several groups have recently developed pH-triggered DNA-based probes or nanomachines [20][21][22][23][24][25][26][27][28][29][30] . Such probes typically exploit DNA secondary structures that display pH-dependence due to the presence of specific protonation sites. These structures include I-motif [21][22][23]26,29,31 , intermolecular triplex DNA 25,28,32 , DNA tweezers 20 and, more recently, the Amotif 33 . Despite the promising and advantageous characteristics of some of these DNA-based nanomachines, which include fast response times and sustained efficiency over several cycles, a drawback inevitably affects their performances: they all respond (with an exception 33a ) over a fixed pH window that typically spans 1.5 to 2 pH units 26,34,33b . These nanomachines, therefore, cannot be adapted to provide a useful output outside these fixed pH-windows.Here we describe a method to rationally design and program pH-triggered DNA-based nanoswitches whose pH-dependence can be finely tuned and modulated over more than 5 units of pH. We created our switches by taking advantage of the wellcharacterized pH sensitivity of the parallel Hoogsteen (T,C)-motif in triplex DNA [34][35][36] . To do so we have designed a DNAbased triplex pH-triggered nanoswitch that consists in a double intramolecular hairpin stabilized with both Watson-Crick (W-C) and parallel Hoogsteen interactions (Fig. 1). More specifically, one hairpin of the triplex nanoswitch is formed by the W-C hybridization of two 10-base complementary portions separated by a 5 base loop. This duplex DNA is then able to form a triplex structure via the formation of a second hairpin through...

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“…Scientists are currently interested in finding ways to mimic enzyme regulatory circuitry outside of the cell 4,5 , not only to increase our knowledge of cellular metabolism but also so that we may create man-made nanoreactors that have potential utility in applications ranging from diagnostics to the production of high-value chemicals [6][7][8] and smart materials 9 . DNA nanostructures are promising scaffolds for use in the organization of molecules on the nanoscale because they can be engineered to site-specifically incorporate functional elements in precise geometries [10][11][12] and to enable nanomechanical control capabilities 13,14 . Examples of such structures include autonomous walkers 15,16 , nanotweezers [17][18][19][20] and nanocages for controlled encapsulation and payload release 21,22 .…”

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confidence: 99%

A DNA tweezer-actuated enzyme nanoreactor

et al. 2013

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The functions of regulatory enzymes are essential to modulating cellular pathways. Here, we report a tweezer-like DNA nanodevice to actuate the activity of an enzyme/cofactor pair. A dehydrogenase and NAD þ cofactor are attached to different arms of the DNA tweezer structure and actuation of enzymatic function is achieved by switching the tweezers between open and closed states. The enzyme/cofactor pair is spatially separated in the open state with inhibited enzyme function, whereas in the closed state, enzyme is activated by the close proximity of the two molecules. The conformational state of the DNA tweezer is controlled by the addition of specific oligonucleotides that serve as the thermodynamic driver (fuel) to trigger the change. Using this approach, several cycles of externally controlled enzyme inhibition and activation are successfully demonstrated. This principle of responsive enzyme nanodevices may be used to regulate other types of enzymes and to introduce feedback or feed-forward control loops.

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Nanomaterials Based on DNA

Cited by 936 publications

References 96 publications

A synthetic icosahedral DNA-based host–cargo complex for functional in vivo imaging

A synthetic icosahedral DNA-based host–cargo complex for functional in vivo imaging

Programmable pH-Triggered DNA Nanoswitches

A DNA tweezer-actuated enzyme nanoreactor

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